BMB Section Seminar: "Protein phosphatases in the regulation of cell cycle progression and cell fate decisions"

Sandra Lopez-Aviles, Group leader, Centre for Molecular Medicine Norway, Faculty of Medicine, UiO

Cell cycle progression and cell fate decisions need to be tightly controlled in order to ensure cell fitness. Protein kinases, in particular cyclin dependent kinase (Cdk) complexes, are key elements in the regulation of cell division. Similarly, cell growth is also subject to strict control by signaling modules of protein kinases that sense nutritional status and other environmental signals. For many years, our attention has been focused in understanding regulation of these protein kinases, and little notice has been paid to the role of protein phosphatases as the counteracting activity that contributes to fine-tuning of these processes. Here, I will present our efforts and approaches to try to understand the role of different phosphatase complexes belonging to the PP2A family regulating mitotic exit and cell differentiation in response to nutritional stress in fission yeast.

While PP2A-B56 (Par1) is required to dephosphorylate Cdk substrates during mitotic exit and to facilitate cell cycle arrest in response to differentiation signals, we have found that of PP2A-B55 (Pab1) prevents cell differentiation. Its loss enhances the expression of differentiation-specific genes and leads to premature conjugation. pab1 deletion brings about a transcriptional profile similar to TORC1 inactivation, and deletion of pab1 overcomes the repression of differentiation genes in cells overexpressing TORC1. Importantly, we show that this effect is mediated by an increased TORC2-AKT (Gad8) signaling. Under nutrient rich conditions PP2A-B55 dephosphorylates Gad8 Ser546, repressing its activity. Conversely, TORC1 inactivation upon starvation leads to the inactivation of PP2A-B55 through the Greatwall-Endosulfin pathway. This results in the activation of Gad8 and the commitment to differentiation. Thus, PP2A-B55 enables a crosstalk between the two TOR complexes that controls cell fate decisions in response to nutrient availability.


Ragnhild Eskeland
Published Feb. 28, 2017 4:38 PM - Last modified Feb. 28, 2017 6:18 PM